1. Field of the Invention
The present invention relates to a cardiomyocyte culture support for controlling the orientation of beating of cardiomyocytes and a method for producing the same.
2. Background Art
A method for myocardium transplantation and for myocardial regenerative therapy wherein somatic stem cells (tissue stem cells) represented by bone marrow cell are selected and transplanted (injected) directly into the heart of a patient has so far been studied. In addition, there have been studies regarding the induction of efficient differentiation of ES cells (embryonic stem cells) of non-human mammals into cardiomyocytes. In recent years, there have also been studies regarding the efficient induction of differentiation of tissue stem cells (e.g., undifferentiated cells contained in fatty tissue) into cardiomyocytes. Thus, the range of cells that are used as sources for myocardium transplantation and myocardial regenerative therapy has been expanding. However, a technique for artificially constructing tissue having functions of the myocardium, such as the function of beating, has not yet been established.
A variety of cell culture supports for forming a sheet-type cell aggregate used for regenerative medicine and the like have been available (e.g., JP Patent Publication (Kokoku) No. 6-104061 B (1994) or Y. Haraguchi et al./Biomaterials 27 (2006) 4765-4774). However, unlike original myocardial tissue, cardiomyocyte sheets produced by the above techniques do not have orientation. In the case of a cardiomyocyte sheet prepared from primary cardiomyocytes (cells released from connective tissue (collected from a baby rat) by collagenase treatment) with the use of a conventional cell culture support, cardiomyocytes account for half of the cells dispersed therein, and vascular endothelial cells, fibroblast cells, and the like account for the other half thereof. A pacemaker cell can be found among 10,000 cardiomyocytes. Cells are electrically connected to each other via a gap junction on a cardiomyocyte sheet formed in a random manner. Accordingly, in a binding stage, the pathway for beating is established in a manner such that electric signals generated from a plurality of pacemaker cells are transmitted through cardiomyocytes and the other cells. In the case of a confluent cell sheet, synchronization takes place via the substantially shortest pathway involving pacemaker cells. However, in such case, electric signal emission lacks orientation. Thus, during beating, the entire sheet repeatedly dilates and contracts; however such dilation and contraction lack orientation.